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Molecular mechanisms of the onset of major depression induced by oligodendrocyte dysfunctions

Research Project

Project/Area Number 16K07073
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionKindai University

Principal Investigator

MIYATA Shingo  近畿大学, 東洋医学研究所, 教授 (70403194)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsオリゴデンドロサイト / タンパクメチル化 / 慢性ストレス / PI3Kシグナル / PI3Kストレス / うつ病
Outline of Final Research Achievements

Repeated stressful events are associated with the onset of major depressive disorder. We previously showed oligodendrocyte-specific activation of the serum/glucocorticoid-regulated kinase 1 cascade, increased expression of axon-myelin adhesion molecules, and elaboration of the oligodendrocytic arbor in the corpus callosum of chronically stressed mice. In the current study, we demonstrate that the Na-K ATPase level and membrane potential of oligodendrocytes were reduced by chronic stress exposure. Furthermore, we found that oligodendrocyte primary cultures subjected to chronic stress resulted in changes of protein arginine methylation levels in several RNA-binding proteins. Our these findings suggest that chronic stress disrupts the organization of the nodes of Ranvier by suppressing the Na-K ATPase levels in oligodendrocytes, and that specific white matter abnormalities are closely associated with major depressive disorder onset.

Academic Significance and Societal Importance of the Research Achievements

本研究成果から、慢性ストレス暴露によるうつ病発症には脳白質オリゴデンドロサイトにおけるアルギニンメチル化レベルの変化と関連するリン酸化シグナルカスケードの活性化が重要な役割を果たす可能性を明らかに出来た事に加えて、オリゴデンドロサイトから軸索への情報伝達機構の重要性についても明らかに出来た。すなわち、脳白質オリゴデンドロサイトでのリン酸化シグナル機能異常をキーとしたうつ病治療のための創薬という臨床応用への基盤を確立できたものと考えられた。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (38 results)

All 2019 2018 2017 2016 Other

All Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 2 results) Presentation (27 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results) Remarks (4 results)

  • [Journal Article] Cytoskeletal signal-regulated oligodendrocyte myelination and remyelination2019

    • Author(s)
      Miyata S
    • Journal Title

      Springer Books/ Myelin-Basic and Clinical Advances

      Volume: 印刷中

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] NDE1 positively regulates oligodendrocyte morphological differentiation2018

    • Author(s)
      Shimizu Shoko、Ishino Yugo、Tohyama Masaya、Miyata Shingo
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 7644-7644

    • DOI

      10.1038/s41598-018-25898-4

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] MARCKSL1 regulates spine formation in the amygdala and controls the hypothalamic-pituitary-adrenal axis and anxiety-like behaviors.2018

    • Author(s)
      Tanaka T, Shimizu S, Ueno M, Fujihara Y, Ikawa M, Miyata S.
    • Journal Title

      EBioMedicine

      Volume: 30 Pages: 62-73

    • DOI

      10.1016/j.ebiom.2018.03.018

    • NAID

      120006957428

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cytoskeletal signal-regulated oligodendrocyte myelination and remyelination.2018

    • Author(s)
      Miyata S
    • Journal Title

      Springer Books/ Myelin-Basic and Clinical Advances

      Volume: ー

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The antistress effect of the Kampo medicine Yokukansan.2017

    • Author(s)
      Shimizu S, Tohyama M, Miyata S.
    • Journal Title

      The Autonomic Nervous System

      Volume: 54 Pages: 21-25

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Molecular mechanisms underlying Kampo Medicine effects.2016

    • Author(s)
      S Miyara
    • Journal Title

      J Jp Soc Psychom Obstet Gynecol

      Volume: 21 Pages: 159-162

    • Related Report
      2016 Research-status Report
  • [Journal Article] ミトコンドリアタンパク質TRAP1機能と ミトコンドリアダイナミクス -脳機能との関わり2016

    • Author(s)
      高村明孝、宮田信吾、遠山正彌、片山泰一
    • Journal Title

      脳21

      Volume: 19 Pages: 230-237

    • Related Report
      2016 Research-status Report
  • [Presentation] 脳内化学物質変化から捉える脳機能と疾患2019

    • Author(s)
      Miyata S.
    • Organizer
      近畿大学サイエンス・シンポジウム 躍動する物質科学・脳科学の最前線-次世代の化学者への提言-
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] フェルラ酸によるヒト皮膚線維芽細胞でのストレス保護効果2018

    • Author(s)
      Miyata S, Shingaki K, Kanazawa S, Shimizu S, Ishino Y, Tohyama M.
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] NDE1はオリゴデンドロサイトの分化を促進する2018

    • Author(s)
      Shimizu S, Ishino Y, Tohyama M, Miyata S.
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 慢性ストレスにより誘発される脳白質異常の分子機構解析2018

    • Author(s)
      Ishino Y, Shimizu S, Tohyama M, Miyata S.
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] うつ病発症に関連するオリゴデンドロサイト接着因子群の解析2018

    • Author(s)
      Miyata S, Yoshikawa K, Shimizu S, Ishino Y, Yamamoto A, Kawakami A, Kaneita M, Yamamoto Y, Tohyama M.
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Effects of Chronic Stress on Sleep in Mice2018

    • Author(s)
      Yasugaki S, Liu CY, Miyata S, Yanagisawa M, Hayashi Y.
    • Organizer
      Tsukuba Global Science Week 2018
    • Related Report
      2018 Annual Research Report
  • [Presentation] 扁桃体における細胞骨格制御因子MARCKSL1は不安様行動を制御する2018

    • Author(s)
      Tanaka T, Miyata S
    • Organizer
      第123回日本解剖学会総会・全国学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] うつ病性障害発症とオリゴデンドロサイト機能2017

    • Author(s)
      宮田信吾、清水尚子、松村彬世、川上あゆみ、鹿島美恵子、遠山正彌
    • Organizer
      第122回日本解剖学会総会・全国学術総会
    • Place of Presentation
      長崎 長崎大学
    • Year and Date
      2017-03-28
    • Related Report
      2016 Research-status Report
  • [Presentation] うつ病発症における脳白質構造変化とオリゴデンドロサイト機能変化の関連2017

    • Author(s)
      Miyata S, Shimizu S, Ishino Y, Yamamoto A, Kawakami A, Tohyama M.
    • Organizer
      2017年度生命科学系学会合同年次大会(ComBio2017)
    • Related Report
      2017 Research-status Report
  • [Presentation] Molecular mechanisms of the onset of neuropsychiatric disorders by the changes in glial functions.2017

    • Author(s)
      Miyata S, Shimizu S, Ishino Y, Tohyama M.
    • Organizer
      The 60th Annual Meeting of the Japanese Society for Neurochemistry
    • Related Report
      2017 Research-status Report
  • [Presentation] Functional analysis of DISC1 binding protein DBZ in oligodendrocyte differentiation.2017

    • Author(s)
      Shimizu S, Miyata S, Tohyama M.
    • Organizer
      The 40th Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2017 Research-status Report
  • [Presentation] The cadherin superfamily proteins in oligodendrocytes in the mouse corpus callosum were changed after chronic stress exposure.2017

    • Author(s)
      Miyata S, Shimizu S, Yamamoto A, Kawakami A, Tohyama M.
    • Organizer
      The 40th Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2017 Research-status Report
  • [Presentation] 慢性ストレスによる脳白質機能変化と大うつ病性障害の関連2017

    • Author(s)
      Miyata S, Shimizu S, Yamamoto A, Kawakami A, Tohyama M.
    • Organizer
      第17回日本抗加齢医学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] microRNAを介した脳内ストレス応答機構への抑肝散の効果2016

    • Author(s)
      宮田信吾、清水尚子、松村彬世、川上あゆみ、遠山正彌
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      横浜 パシフィコ横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] Association between stress-induced Ranvier nodes structural abnormalities and reduced oligodendrocyte activity in major depressive disorder2016

    • Author(s)
      S. Miyata, S. Shimizu, T. Tanaka, M. Tohyama.
    • Organizer
      Neuroscience 2016, SfN's 46th annual meeting
    • Place of Presentation
      米国 San Diego Convention Center
    • Year and Date
      2016-11-12
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] うつ病発症に関わる脳白質オリゴデンドロサイトの機能変化2016

    • Author(s)
      宮田信吾、清水尚子、田中貴士、松村彬世、川上あゆみ、遠山正彌
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台 仙台国際センター
    • Year and Date
      2016-09-25
    • Related Report
      2016 Research-status Report
  • [Presentation] 精神疾患関連分子によるオリゴデンドロサイト発達制御2016

    • Author(s)
      宮田信吾、清水尚子、服部剛志、遠山正彌
    • Organizer
      第38回日本生物学的精神医学会・第59回日本神経化学会大会 合同年会
    • Place of Presentation
      福岡 福岡国際会議場
    • Year and Date
      2016-09-08
    • Related Report
      2016 Research-status Report
  • [Presentation] Functional analysis of DISC1 binding protein DBZ in oligodendrocyte differentiation2016

    • Author(s)
      清水尚子、田中貴士、遠山正彌、宮田信吾
    • Organizer
      第38回日本生物学的精神医学会・第59回日本神経化学会大会 合同年会
    • Place of Presentation
      福岡 福岡国際会議場
    • Year and Date
      2016-09-08
    • Related Report
      2016 Research-status Report
  • [Presentation] Overexpression of MARCKSL1 induces anxiety-like behavior via hyperactivation of the basolateral amygdala2016

    • Author(s)
      田中貴士、清水尚子、遠山正彌、宮田信吾
    • Organizer
      第38回日本生物学的精神医学会・第59回日本神経化学会大会 合同年会
    • Place of Presentation
      福岡 福岡国際会議場
    • Year and Date
      2016-09-08
    • Related Report
      2016 Research-status Report
  • [Presentation] Structural alterations and functional declines of the nodes of Ranvier by exposed repeated stressful events is associated with the onset of major depressive disorder2016

    • Author(s)
      S Miyata, S Shimizu, T Tanaka, A Matsumura, A Kawakami, M Tohyama.
    • Organizer
      第39回日本神経科学大会
    • Place of Presentation
      横浜 パシフィコ横浜
    • Year and Date
      2016-07-20
    • Related Report
      2016 Research-status Report
  • [Presentation] Functional analysis of DISC1 binding protein DBZ in oligodendrocyte differentiation2016

    • Author(s)
      S Shimizu, S Miyata, T Tanaka, M Tohyama.
    • Organizer
      第39回日本神経科学大会
    • Place of Presentation
      横浜 パシフィコ横浜
    • Year and Date
      2016-07-20
    • Related Report
      2016 Research-status Report
  • [Presentation] MARCKS-like 1 protein is associated with the pathogenesis of anxiety and depressive disorders2016

    • Author(s)
      T Tanaka, S Miyata, S Shimizu, M Tohyama.
    • Organizer
      第39回日本神経科学大会
    • Place of Presentation
      横浜 パシフィコ横浜
    • Year and Date
      2016-07-20
    • Related Report
      2016 Research-status Report
  • [Presentation] PRMT1-dependent arginine methylation on hnRNP K regulates dendritic transport of alpha CaMKII mRNA2016

    • Author(s)
      Y Mori, T Iguchi, S Miyata, M Tohyama, M Sato.
    • Organizer
      第39回日本神経科学大会
    • Place of Presentation
      横浜 パシフィコ横浜
    • Year and Date
      2016-07-20
    • Related Report
      2016 Research-status Report
  • [Presentation] The Kampo medicine Yokukansan normalizes glucocorticoid receptor protein expression in the mice brain by regulating microRNA expressions after stress exposure2016

    • Author(s)
      S Miyata, S Shimizu, T Tanaka, M Tohyama.
    • Organizer
      RNA 2016, The RNA Society of Japan 18th Annual Meeting AND The 21st Annual Meeting of the RNA Society,
    • Place of Presentation
      京都 国際会議場
    • Year and Date
      2016-06-28
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Functional analysis of DISC1-binding zinc finger protein (DBZ) during oligodendrocyte differentiation2016

    • Author(s)
      清水尚子、遠山正彌、宮田信吾
    • Organizer
      第21回グリア研究会
    • Place of Presentation
      大阪 千里ライフサイエンスセンター
    • Related Report
      2016 Research-status Report
  • [Presentation] オリゴデンドロサイトにおける統合失調症関連因子の機能解析2016

    • Author(s)
      清水尚子、遠山正彌、宮田信吾
    • Organizer
      第92回日本解剖学会近畿支部学術集会
    • Place of Presentation
      大阪 近畿大学
    • Related Report
      2016 Research-status Report
  • [Presentation] 脳白質機能変化とうつ病発症の関連性~マウスモデル動物からヒトうつ病患者まで~2016

    • Author(s)
      宮田信吾
    • Organizer
      神戸大学大学院医学系研究科 先端医学トピックス
    • Place of Presentation
      神戸 神戸大学
    • Related Report
      2016 Research-status Report
    • Invited
  • [Remarks] 近畿大学 東洋医学研究所 分子脳科学研究部門(基礎研究部門)

    • URL

      http://www.med.kindai.ac.jp/toyo/study/index.html

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
  • [Remarks] 近畿大学 東洋医学研究所 分子脳科学研究部門(基礎研究部門)研究成果

    • URL

      http://www.med.kindai.ac.jp/toyo/study/results.html

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
  • [Remarks] 近畿大学 東洋医学研究所 分子脳科学研究部門(基礎研究部門)

    • URL

      http://www.med.kindai.ac.jp/toyo/study/index.html

    • Related Report
      2016 Research-status Report
  • [Remarks] 近畿大学 東洋医学研究所 分子脳科学研究部門(基礎研究部門)研究成果

    • URL

      http://www.med.kindai.ac.jp/toyo/study/results.html

    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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